Month: October 2022

Computed Properties of C4H2Cl2N2In 2020 ,《Discovery of novel 2,4-disubstituted pyrimidines as Aurora kinase inhibitors》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Xu, Yu; Hao, Shu-Yi; Zhang, Xiu-Juan; Li, Wen-Bo; Qiao, Xue-Peng; Wang, Zi-Xiao; Chen, Shi-Wu. The article conveys some information:

In order to explore novel Aurora kinase inhibitors, a series of novel 2,4-disubstituted pyrimidines were designed, synthesized and evaluated their in vitro anti-proliferative activities against a panel of cancerous cell lines (A549, HCT-116 and MCF-7). Among them, compound 12a (I) showed moderate to high anti-proliferative activities against A549 (IC50 = 12.05 ± 0.45μM), HCT-116 (IC50 = 1.31 ± 0.41μM) and MCF-7 (IC50 = 20.53 ± 6.13μM) cells, as well as the Aurora A and Aurora B inhibitory activities with the IC50 values of 309 nM and 293 nM, resp. Furthermore, compound 12a induced apoptosis by upregulating the pro-apoptotic proteins Bax and decreased the anti-apoptotic protein Bcl-xl in HCT-116 cells. Moreover, the mol. docking study showed that compound 12a had good binding modes with Aurora A and Aurora B and the bioinformatics prediction discovered that compound 12a exhibited good drug likeness using SwissADME. Taken together, these results indicated that 12a may be a potential anticancer compound that was worthy of further development as Aurora kinase inhibitor. The experimental process involved the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1Computed Properties of C4H2Cl2N2)

2,4-Dichloropyrimidine(cas: 3934-20-1) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Computed Properties of C4H2Cl2N2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Category: pyrimidinesIn 2017 ,《Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase》 appeared in Journal of Medicinal Chemistry. The author of the article were Brough, Paul A.; Baker, Lisa; Bedford, Simon; Brown, Kirsten; Chavda, Seema; Chell, Victoria; D’Alessandro, Jalanie; Davies, Nicholas G. M.; Davis, Ben; Le Strat, Loic; Macias, Alba T.; Maddox, Daniel; Mahon, Patrick C.; Massey, Andrew J.; Matassova, Natalia; McKenna, Sean; Moore, Jonathan D.; Murray, James B.; Northfield, Christopher J.; Parry, Charles; Parsons, Rachel; Roughley, Stephen D.; Shaw, Terry; Simmonite, Heather; Stokes, Stephen; Surgenor, Allan; Stefaniak, Emma; Robertson, Alan; Wang, Yikang; Webb, Paul; Whitehead, Neil; Wood, Mike. The article conveys some information:

Libraries of non-purified resorcinol amide derivatives were screened by surface plasmon resonance (SPR) to determine the binding dissociation constant (off-rate, kd) for compounds binding to the pyruvate dehydrogenase kinase (PDHK) enzyme. Parallel off-rate measurements against HSP90 and application of structure-based drug design enabled rapid hit to lead progression in a program to identify pan-isoform ATP-competitive inhibitors of PDHK. Lead optimization identified selective sub-100-nM inhibitors of the enzyme which significantly reduced phosphorylation of the E1α subunit in the PC3 cancer cell line in vitro. In the experimental materials used by the author, we found 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Category: pyrimidines)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. Category: pyrimidinesThey have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

《Study on the preparation of heteroaryl substituted enamines. A simple synthesis of heteroaryl substituted acetaldoximes from enamines》 was written by Copar, Anton; Stanovnik, Branko; Tisler, Miha. Safety of 2-Methoxy-4-methylpyrimidine And the article was included in Journal of Heterocyclic Chemistry on April 30 ,1996. The article conveys some information:

A comparative study of the reactivity of Me groups towards N,N-dimethylformamide di-Me acetal and tert-butoxybis(dimethylamino)methane was carried out on Me substituted six-membered nitrogen containing heterocycles to give enamines, which were easily transformed to oximes by treating with hydroxylamine hydrochloride in methanol. Most of them were isolated as (E,Z)-oximes of heteroarylacetaldehyde, but 5-(1,2,4-triazinyl) substituted derivatives were isolated as (E,Z)-oximes of 2,5-dihydro-1,2,4-triazin-(Z)-5-ylideneacetaldehyde. Oximes were finally transformed to the corresponding acetontriles and 3-(dimethylamino)acrylonitriles. In the experimental materials used by the author, we found 2-Methoxy-4-methylpyrimidine(cas: 14001-60-6Safety of 2-Methoxy-4-methylpyrimidine)

2-Methoxy-4-methylpyrimidine(cas: 14001-60-6) is a member of ether. When aromatic ethers are exposed to halogen in the presence or absence of a catalyst, they undergo halogenation, such as bromination.Safety of 2-Methoxy-4-methylpyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Electric Literature of C17H16N2O5On May 31, 2002, Kumamoto, Hiroki; Tanaka, Hiromichi published an article in Journal of Organic Chemistry. The article was 《Simple Entry to 3′-Substituted Analogues of Anti-HIV Agent Stavudine Based on an Anionic O → C Stannyl Migration》. The article mentions the following:

Reaction of 5′-O-protected derivatives of the anti-HIV agent stavudine (d4T) with LTMP was investigated with the aim to lithiate the vinylic hydrogens (H-3′ and H-2′). When the lithiation of the 5′-O-tert-butyldiphenylsilyl derivative I was carried out in the presence of HMPA, an anionic silyl migration took place to give the 3′-C-silylated product II. The stannyl version of this reaction was found to be also possible, which has disclosed a highly simple entry to the d4T analogs variously substituted at the 3′-position by manipulating the 3′-C-stannyl d4T as a common intermediate. In the experiment, the researchers used many compounds, for example, ((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate(cas: 122567-97-9Electric Literature of C17H16N2O5)

((2S,5R)-5-(5-Methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,5-dihydrofuran-2-yl)methyl benzoate(cas: 122567-97-9) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Electric Literature of C17H16N2O5

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Formula: C5H6N2O3On September 8, 2022 ,《Fragment Ligands of the m6A-RNA Reader YTHDF2》 was published in ACS Medicinal Chemistry Letters. The article was written by Nai, Francesco; Nachawati, Raed; Zalesak, Frantisek; Wang, Xiang; Li, Yaozong; Caflisch, Amedeo. The article contains the following contents:

17 Small-mol. ligands that compete with N6-methyladenosine (m6A) for binding to the m6A-reader domain of YTHDF2 (YT521-B homol. domain family 2) was reported. Their binding mode at high resolution was determined by X-ray crystallog. and their affinity was quantified by a fluorescence-based binding assay. 6-Cyclopropyluracil and a pyrazolopyrimidine derivative had favorable ligand efficiencies of 0.47 and 0.38 kcal mol-1 per non-hydrogen atom, resp. They represent useful starting points for hit optimization. In addition to this study using 6-Methoxypyrimidine-2,4(1H,3H)-dione, there are many other studies that have used 6-Methoxypyrimidine-2,4(1H,3H)-dione(cas: 29458-38-6Formula: C5H6N2O3) was used in this study.

6-Methoxypyrimidine-2,4(1H,3H)-dione(cas: 29458-38-6) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Formula: C5H6N2O3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

COA of Formula: C11H8N2O4On October 21, 2004 ,《HCV NS5b RNA-Dependent RNA Polymerase Inhibitors: From α,γ-Diketoacids to 4,5-Dihydroxypyrimidine- or 3-Methyl-5- hydroxypyrimidinonecarboxylic Acids. Design and Synthesis》 was published in Journal of Medicinal Chemistry. The article was written by Summa, Vincenzo; Petrocchi, Alessia; Matassa, Victor G.; Taliani, Marina; Laufer, Ralph; De Francesco, Raffaele; Altamura, Sergio; Pace, Paola. The article contains the following contents:

A new class of the HCV NS5b RNA-dependent RNA polymerase inhibitors, the dihyroxypyrimidinecarboxylic acid derivative, was designed from a diketoacid and meconic acid derivative discovered by screening. Mechanism of action and essential moieties required for activity were identified. The corresponding N-methylpyrimidinone was also prepared; both classes are novel, reversible, and selective inhibitors of the HCV NS5b polymerase with improved druglike characteristics. The results came from multiple reactions, including the reaction of 5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2COA of Formula: C11H8N2O4)

5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid(cas: 62222-38-2) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. COA of Formula: C11H8N2O4They have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Edo, Kiyoto; Sakamoto, Takao; Yamanaka, Hiroshi published their research in Chemical & Pharmaceutical Bulletin on December 31 ,1978. The article was titled 《Studies on pyrimidine derivatives. IX. Coupling reaction of mono-substituted acetylenes with iodopyrimidines》.Synthetic Route of C6H6BrClN2 The article contains the following contents:

Pyrimidine derivatives containing an acetylenic side chain were prepared by reaction of alkyl or Ph acetylenes with 2-, 4-, and 5-iodopyrimidines in the presence of Pd(PPh3)2Cl2. When HCCCH2OH was used, the reaction yield decreased. The reaction proceeded with 2,4-diiodo- and 4,6-diiodopyrimidines to give dialkynyl derivatives This acetylene coupling reaction was applicable to the preparation of 4-quinazoline derivatives The results came from multiple reactions, including the reaction of 5-Bromo-4-chloro-2,6-dimethylpyrimidine(cas: 69696-35-1Synthetic Route of C6H6BrClN2)

5-Bromo-4-chloro-2,6-dimethylpyrimidine(cas: 69696-35-1) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Synthetic Route of C6H6BrClN2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Reactions of pyrimidin-5-yllithium compounds》 were Caton, M. P. L.; Grant, M. S.; Pain, D. L.; Slack, R.. And the article was published in Journal of the Chemical Society in 1965. Category: pyrimidines The author mentioned the following in the article:

Pyrimidin-5-yllithium compounds, mostly having alkoxy substituents, reacted with CO2, HCONMe2, and S, forming, resp., carboxylic acids, aldehydes, and polysulfides. The last were reduced and converted in situ into (pyrimidin-5-ylthio)alkanoic acids. Preparations of pyrimidin-5-ylacetic acids and of 5-bromo-2-formylpyrimidine are also described. The experimental process involved the reaction of 5-Bromo-4,6-dimethoxy-2-methylpyrimidine(cas: 4319-83-9Category: pyrimidines)

5-Bromo-4,6-dimethoxy-2-methylpyrimidine(cas: 4319-83-9) is a member of ether. When aromatic ethers are exposed to halogen in the presence or absence of a catalyst, they undergo halogenation, such as bromination.Category: pyrimidines

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

The author of 《Syntheses of heterocyclic compounds. CDXCI. Pyrimidine derivatives. V. Abnormal condensation products of 4-amino-6-chloro-2-methoxypyrimidine with p-nitrobenzenesulfonyl chloride》 were Okui, Kiyoshi; Ito, Kiyohiko; Koizumi, Masuo; Fukumoto, Keiichiro; Kametani, Tetsuji. And the article was published in Journal of Heterocyclic Chemistry in 1972. HPLC of Formula: 3286-56-4 The author mentioned the following in the article:

Condensation of 4-amino-6-chloro-2-methoxypyrimidine with p-O2NC6H4SO2Cl gave, in addition to 6-chloro-2-methoxy-4-(p-nitrobenzenesulfonamido)pyrimidine (I), two abnormal by-products, 1-[2-methoxy-4-(p-nitrobenzenesulfonamido)pyrimidin-6-yl]pyridinium N,N-betaine (II) and N-(p-nitrobenzenesulfonyl)-β-ureido-β-pyridinium arcylamide N,N-betaine (III). The experimental part of the paper was very detailed, including the reaction process of 6-Chloro-2-ethoxypyrimidin-4-amine(cas: 3286-56-4HPLC of Formula: 3286-56-4)

6-Chloro-2-ethoxypyrimidin-4-amine(cas: 3286-56-4) belongs to anime. Reaction with nitrous acid (HNO2), which functions as an acylating agent that is a source of the nitrosyl group (―NO), converts aliphatic primary amines to nitrogen and mixtures of alkenes and alcohols corresponding to the alkyl group in a complex process. This reaction has been used for analytical determination of primary amino groups in a procedure known as the Van Slyke method.HPLC of Formula: 3286-56-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

In 2014,Odingo, Joshua; O’Malley, Theresa; Kesicki, Edward A.; Alling, Torey; Bailey, Mai Ann; Early, Julie; Ollinger, Juliane; Dalai, Suryakanta; Kumar, Naresh; Singh, Ravindra Vikram; Hipskind, Philip A.; Cramer, Jeffrey W.; Ioerger, Thomas; Sacchettini, James; Vickers, Richard; Parish, Tanya published 《Synthesis and evaluation of the 2,4-diaminoquinazoline series as anti-tubercular agents》.Bioorganic & Medicinal Chemistry published the findings.HPLC of Formula: 90213-66-4 The information in the text is summarized as follows:

The 2,4-diaminoquinazoline class of compounds has previously been identified as an effective inhibitor of Mycobacterium tuberculosis growth. The authors conducted an extensive evaluation of the series for its potential as a lead candidate for tuberculosis drug discovery. Three segments of the representative mol. N-(4-fluorobenzyl)-2-(piperidin-1-yl)quinazolin-4-amine were examined systematically to explore structure-activity relationships influencing potency. The authors determined that the benzylic amine at the 4-position, the piperidine at 2-position and the N-1 (but not N-3) are key activity determinants. The 3-deaza analog retained similar activity to the parent mol. Biol. activity was not dependent on iron or carbon source availability. The authors demonstrated through pharmacokinetic studies in rats that good in vivo compound exposure is achievable. A representative compound demonstrated bactericidal activity against both replicating and nonreplicating M. tuberculosis. The authors isolated and sequenced M. tuberculosis mutants resistant to this compound and observed mutations in Rv3161c, a gene predicted to encode a dioxygenase, suggesting that the compound may act as a prodrug. In the experimental materials used by the author, we found 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4HPLC of Formula: 90213-66-4)

2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine derivatives also play an important role in drug development, either in concert with other compounds or on their own. HPLC of Formula: 90213-66-4They have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia